This is a new K08 application, the purpose of which is to provide training and a mentored research environment for the candidate, Dr. Juan Carlos Q. Velez, at the Medical University of South Carolina. MUSC is part of South Carolina's largest medical complex with 140,000 ft2 dedicated to research laboratory space and a multidisciplinary University Research Resource Facility (URRF) that contains shared resources available to investigators including: Advanced Image Analysis; Gene targeting and Knockout Mouse Facility; Nuclear Magnetic Resonance Facility, and an established Mass Spectrometry Facility. Candidate. The candidate is a new full-time tenure-track assistant professor in the Division of Nephrology, at the MUSC. He is an up-and-coming young clinician-scientist that has a track record of two awards in basic science research during his early career and one recent first-author publication in a prestigious peer-reviewed journal. He possesses professional qualities highly suited for KO8 sponsorship. Dr. Velez has outlined a plan to develop a successful independently funded laboratory and to gain experience necessary to maintain a productive scientific career relevant to kidney research. To ensure these goals are met, Dr. Velez has assembled a highly qualified mentorship committee of scientists who have extensive track records in obtaining extramural funding and maintaining successful research laboratories. Research Proposal. The proposal has been designed to include a focused hypothesis-driven series of experiments that will yield insight into mechanisms of hormonal regulation within the kidney glomerulus and their relationship with pathways that lead to progressive kidney diseases. Specifically, the proposal is focused on examining the balance between intraglomerular angiotensin-II and other angiotensin metabolites and the role that glomerular podocytes play in that system. The goal of the research proposal is to establish a foundation of technical knowledge and expertise by which a long-term research program can be established. PUBLIC HEALTH RELEVANCE: The studies outlined herein will add to the understanding of the existing mechanisms within the kidney to counterbalance the actions of the hormone angiotensin-II. Twenty million American have chronic kidney disease and many others are on risk of acquiring it. Pharmacological blockade of angiotensin-II constitutes the only FDA-approved therapy available. Despite receiving this therapy, a significant percentage of the affected patients continue to progress to the end-stage form of the disease. Better understanding of the mechanisms of in the kidney should lead to therapies that can directly target. These therapies would improve both quality and length of life of affected individuals.